404 - Nitrosylation of Vesicular Transporters in Brain of Amyloid Precursor Protein/presenilin 1 Double Transgenic Mice

Abstract

Nitric oxide can attack thiols of protein cysteine residues and induce cysteine S-nitrosylation. Cholinergic and glutamatergic systems are dysregulated in Alzheimer’s disease (AD). Vesicular acetylcholine transporter (VAChT) and vesicular glutamate transporter 1 (VGLUT1) are important in packaging acetylcholine and glutamate into vesicles that is an important step for neurotransmission. Previously we found that VAChT and VGLUT1 can be nitrosylated and this nitrosylation inhibits vesicular uptake of acetylcholine and glutamate. To understand the role of VAChT and VGLUT1 nitrosylation in the pathophysiological development of AD, we analyzed nitrosylation to VAChT and VGLUT1 in brain of amyloid precursor protein (APP) and presenilin 1 (PS1) transgenic mice, an animal model for AD. We found that 9 and 12 month old APP/PS1 mice showed memory deficit. We further found that total protein nitrosylation was increased in frontal cortex and hippocampus of 9 and 12 month old APP/PS1 mice when compared to wild type mice. Although nitrosylation of VAChT and VGLUT1 was not changed in hippocampus, nitrosylation of VAChT and VGLUT1 was increased in frontal cortex of 9 and 12 month old APP/PS1 mice. These findings suggest that nitrosylation of VAChT and VGLUT1 may be associated with dysfunctional acetylcholinergic and glutamatergic neurotransmission in AD.